BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases reported.CASE SUMMARY This study reports a 51-year-old man with primary SCC of the renal parenchyma.The pat...BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases reported.CASE SUMMARY This study reports a 51-year-old man with primary SCC of the renal parenchyma.The patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross hematuria.SCC antigen(SCCA)levels were elevated,and imaging revealed a renal mass with associated calculi.The patient underwent laparoscopic unilateral nephrectomy and lymph node dissection.Postoperative pathology confirmed highly differentiated SCC with necrosis in the right renal parenchyma,with negative renal pelvis and ureter.The pathological stage was Pt3aN1M0.Four months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena cava.The patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease progression.CONCLUSION We report a case of primary SCC of the renal parenchyma,a rare renal malignancy.The clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis challenging.According to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum SCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
BACKGROUND In recent years,the global prevalence of gastric cancer(GC)has witnessed a progressive decrease,accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma(GSRCC).As precision medici...BACKGROUND In recent years,the global prevalence of gastric cancer(GC)has witnessed a progressive decrease,accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma(GSRCC).As precision medicine concepts progress,GSRCC,a distinct sub-type of GC,has drawn considerable attention from researchers.However,there still persist some controversies regarding the associated research findings.AIM To summarize the current obstacles and potential future directions for research on GSRCC.METHODS To begin with,all literature related to GSRCC published from January 1,2004 to December 31,2023 was subjected to bibliometric analysis in this article.Additionally,this paper analyzed the research data using CiteSpace,GraphPad Prism v8.0.2,and VOSviewer,which was obtained from the Web of Science Core Collection database.The analysis results were visually represented.RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC,including cited references,authors,journals,countries,institutions,and keywords.The popular keywords and clusters contain"prognosis","survival","expression","histology",and"chemotherapy".CONCLUSION The prognosis,precise definition and classification,as well as chemoresistance of GSRCC,continue to be crucial areas of ongoing research,whose directions are closely tied to advancements in molecular biology research on GSRCC.展开更多
BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by...BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours,such as lung cancer,oesophageal cancer or mediastinum tumours.Renal cell carcinoma(RCC),accounting for 2%to 3%of all tumours,is a common malignant tumour of the urinary system.Renal clear cell carcinoma(RCCC)constitutes the predominant pathological subtype of RCC,comprising approximately 70%to 80%of all RCC cases.RCCC can spread and metastasise through arterial,venous and lymphatic circulation to almost all organs of the body.Moreover,lung,bone,liver,brain and local recurrence are the most common metastatic neoplasms of RCCC.However,EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer.CASE SUMMARY A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough.The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung,and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe.Therefore,the patient underwent thoracoscopic left superior lobe wedge resection,and pathology confirmed EBM from the RCCC.CONCLUSION EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage.If a bronchial tumour is found in a patient with RCCC,the possibility of bronchial metastatic cancer should be considered.展开更多
Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study...Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study aimed to identify differences in the proliferative indices among variants of cBCC and cSCC diagnosed at a tertiary healthcare center. Method: Skin biopsies histologically diagnosed as cBCC and cSCC between 2012 and 2018 at the Federal Medical Centre (FMC) Umuahia, Abia State, Nigeria, were analyzed. Archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were retrieved along with clinical data, and were prepared on charged microscope slides and the immunohistochemical staining was carried out. The primary antibody used in this study was clone BioCare CRM325C (RM) and adenotonsillar tissue blocks/slides served as positive controls. Ki-67 immunohistochemistry was performed on fresh 4µm sections of the tumor specimens. Results: The application of Ki-67 immunoperoxidase on both BCC and SCC cohort, yielded an intense observable brownish nuclear stain in areas of dense proliferating tumour cells on both cutaneous tumours. The average Ki-67 index for all cSCC cases was 24.7%, with a range of 2.3% - 80%, while the mean for cBCC was 15.8%, ranging from 1.2% - 45.6%. Variants with high proliferative indices were observed in 11.9% of cBCC cases and 29.1% of cSCC cases. Among the low proliferative index category, cSCC accounted for 5.4%, while cBCC represented 14.3%. For mild proliferative indices, cSCC cases made up 7.3% and cBCC, 11.9%. The majority of cases showed moderate proliferative indices, with 61.9% for cBCC and 58.2% for cSCC. Overall, there was a significant difference in proliferative indices between cSCC, cBCC, and their variants. Conclusion: The study found a significantly higher rate of cell proliferation, measured by Ki-67 immunostaining, in cSCC and its variants compared to cBCC. However, certain variants of cBCC also exhibited high Ki-67 expression, indicating they can be as aggressive as some cSCC variants.展开更多
As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major h...As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.展开更多
Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ES...Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.展开更多
BACKGROUND Cases of severe inflammatory renal disease and renal cell carcinoma(RCC)that occur simultaneously in the same kidney have been occasionally reported.However,extrarenal RCC that does not originate from the n...BACKGROUND Cases of severe inflammatory renal disease and renal cell carcinoma(RCC)that occur simultaneously in the same kidney have been occasionally reported.However,extrarenal RCC that does not originate from the native kidney has rarely been reported.To our knowledge,this is the first reported case of RCC developing in the ipsilateral retroperitoneal space after a simple nephrectomy(SN)for inflammatory renal disease.CASE SUMMARY A 63-year-old woman was referred to our hospital following the incidental discovery of a left retroperitoneal mass without specific symptoms.Her medical history revealed a left SN 27 years ago due to a renal abscess.Magnetic resonance imaging of the abdomen revealed three oval masses in the left retroperitoneum.The masses were successfully excised,and subsequent pathology confirmed papillary RCC.After surgery,the patient remained disease-free for 11 years without adjuvant therapy.CONCLUSION Clinicians should be vigilant of RCC in patients with retroperitoneal masses,especially after SN for inflammatory renal disease.展开更多
BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multi...BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts,often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage.A total of 38 kidneys were excised from 19 patients,with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months.Eight patients underwent open nephrectomies,and 11 underwent hand-assisted laparoscopic nephrec-tomies.RCC was detected in 15.8%of kidneys,affecting 21.1%of patients.Two patients had multifocal RCC in both kidneys.All RCC cases were pT1 stage,with the largest lesion averaging 16.5 mm in diameter.The average operative duration was 120 minutes,with intraoperative blood loss averaging 184.2 mL.Five patients required blood transfusions.Postoperative complications occurred in five patients,with a mean hospital stay of 17.1 days.The mean follow-up period was 28.1 months.CONCLUSION The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone.Thus,clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD,particularly those on dialysis.展开更多
Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One k...Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.展开更多
Background:The role of Claudin-1 in tongue squamous cell carcinoma(TSCC)metastasis needs further clarification,particularly its impact on cell migration.Herein,our study aims to investigate the role of Claudin-1 in TS...Background:The role of Claudin-1 in tongue squamous cell carcinoma(TSCC)metastasis needs further clarification,particularly its impact on cell migration.Herein,our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms.Methods:36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1.Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells.Claudin-1 knockdown cell lines were established using short hairpin RNA transfection.Migration effects were assessed through wound healing assays.Furthermore,the expression of EMTassociated molecules was measured via western blotting.Results:Claudin-1 expression decreased as TSCC malignancy increased.Adenosine monophosphate–activated protein kinase(AMPK)activation led to increased Claudin-1 expression and membrane translocation,inhibiting TSCC cell migration and epithelial–mesenchymal transition(EMT).Conversely,Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation.Conclusions:Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.展开更多
Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was ...Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.展开更多
Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac...Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.展开更多
Objective:two new cases of temporal bone squamous cell carcinoma(TBSCC)with a bilateral occurrence are presented.Furthermore,a review of the literature was performed and the yearly incidence was calculated.Methods:A s...Objective:two new cases of temporal bone squamous cell carcinoma(TBSCC)with a bilateral occurrence are presented.Furthermore,a review of the literature was performed and the yearly incidence was calculated.Methods:A systematic review of the literature was conducted using PRISMA guidelines.Results:Twenty-two more cases were found in literature.With a total of 24 cases,the calculated yearly incidence of bilateral TBSCC is 49:10^12 A history of chronic otitis or regional radiotherapy was found in respectively 50%and 12%of patients.In nine patients,the tumors developed synchronously(within 6 months)and in 13 metachronously.Conclusions:The calculated incidence is 89 times higher than mathematically expected considering the incidence of unilateral cases.An explanation might be a history of chronic otitis or prior radiotherapy.The tumor staging of both the first tumor group and the contralateral tumor group are similar to unilateral temporal bone squamous cell carcinoma series.展开更多
BACKGROUND The early diagnosis rate of esophageal cancer(EC),one of the most prevalent digestive tract cancers worldwide,remains low.AIM To investigate the utility of plasma SHOX2,SEPTIN9,EPO,and RNF180 methylation in...BACKGROUND The early diagnosis rate of esophageal cancer(EC),one of the most prevalent digestive tract cancers worldwide,remains low.AIM To investigate the utility of plasma SHOX2,SEPTIN9,EPO,and RNF180 methylation in the clinical diagnosis and monitoring of EC.Plasma samples were collected from 210 patients at Hubei Cancer Hospital,and TaqMan polymerase chain reaction was employed to detect plasma SHOX2,SEPTIN9,RNF180,and EPO methylation.The area under the curve was used to estimate their diagnostic value for EC.Cox and logistic regression analyses were used to estimate the independent screening risk factors for patients with EC.RESULTS The sensitivity and specificity of combined assessment of plasma SHOX2,SEPTIN9,RNF180,and EPO methylation for adenocarcinoma,squamous cell carcinoma(SCC),and EC detection were 66.67%and 86.27%,77.40%and 85.29%,and 76.19%and 86.27%,respectively;the area under the curve values for diagnosing adenocarcinoma,SCC,and EC were 0.737[95%confidence interval(CI):0.584–0.89],0.824(95%CI:0.775–0.891),and 0.864(95%CI:0.809–0.92),respectively.CONCLUSION According to our findings,plasma SHOX2,SEPTIN9,RNF180,and EPO methylation exhibits appreciated sensitivity for diagnosing EC.The precise measurement of plasma SHOX2,SEPTIN9,RNF180,and EPO methylation can improve EC diagnosis and therapy efficacy monitoring.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is ...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.展开更多
Objective:This review aimed to summarize the role of the Hippo signaling pathway in renal cell carcinoma (RCC), a urologic malignancy with subtle initial symptoms and high mortality rates due to metastatic RCC. The Hi...Objective:This review aimed to summarize the role of the Hippo signaling pathway in renal cell carcinoma (RCC), a urologic malignancy with subtle initial symptoms and high mortality rates due to metastatic RCC. The Hippo signaling pathway, which regulates tissue and organ sizes, plays a crucial role in RCC progression and metastasis. Understanding the involvement of the Hippo signaling pathway in RCC provides valuable insights for the development of targeted therapies and improved patient outcomes.Methods:In this review, we explored the impact of the Hippo signaling pathway on RCC. Through an analysis of existing literature, we examined its role in RCC progression and metastasis. Additionally, we discussed potential therapeutic strategies targeting the Hippo pathway for inhibiting RCC cell growth and invasion. We also highlighted the importance of investigating interactions between the Hippo pathway and other signaling pathways such as Wnt, transforming growth factor-beta, and PI3K/AKT, which may uncover additional therapeutic targets.Results:The Hippo signaling pathway has shown promise as a target for inhibiting RCC cell growth and invasion. Studies have demonstrated its dysregulation in RCC, with altered expression of key components such as yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ). Targeting the Hippo pathway has been associated with suppressed tumor growth and metastasis in preclinical models of RCC. Furthermore, investigating crosstalk between the Hippo pathway and other signaling pathways has revealed potential synergistic effects that could be exploited for therapeutic interventions.Conclusion:Understanding the role of the Hippo signaling pathway in RCC is of paramount importance. Elucidating its functions and molecular interactions contributes to RCC diagnosis, treatment, and the discovery of novel mechanisms. This knowledge informs the development of innovative therapeutic strategies and opens new avenues for research in RCC. Further investigations are warranted to fully comprehend the complex interplay between the Hippo pathway and other signaling pathways, ultimately leading to improved outcomes for RCC patients.展开更多
BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively hig...BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.展开更多
Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selec...Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.展开更多
Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression....Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.展开更多
文摘BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases reported.CASE SUMMARY This study reports a 51-year-old man with primary SCC of the renal parenchyma.The patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross hematuria.SCC antigen(SCCA)levels were elevated,and imaging revealed a renal mass with associated calculi.The patient underwent laparoscopic unilateral nephrectomy and lymph node dissection.Postoperative pathology confirmed highly differentiated SCC with necrosis in the right renal parenchyma,with negative renal pelvis and ureter.The pathological stage was Pt3aN1M0.Four months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena cava.The patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease progression.CONCLUSION We report a case of primary SCC of the renal parenchyma,a rare renal malignancy.The clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis challenging.According to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum SCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金Supported by National Natural Science Foundation of China,No.82073192,and No.82273231Beijing Science and Technology Program,No.Z221100007422125.
文摘BACKGROUND In recent years,the global prevalence of gastric cancer(GC)has witnessed a progressive decrease,accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma(GSRCC).As precision medicine concepts progress,GSRCC,a distinct sub-type of GC,has drawn considerable attention from researchers.However,there still persist some controversies regarding the associated research findings.AIM To summarize the current obstacles and potential future directions for research on GSRCC.METHODS To begin with,all literature related to GSRCC published from January 1,2004 to December 31,2023 was subjected to bibliometric analysis in this article.Additionally,this paper analyzed the research data using CiteSpace,GraphPad Prism v8.0.2,and VOSviewer,which was obtained from the Web of Science Core Collection database.The analysis results were visually represented.RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC,including cited references,authors,journals,countries,institutions,and keywords.The popular keywords and clusters contain"prognosis","survival","expression","histology",and"chemotherapy".CONCLUSION The prognosis,precise definition and classification,as well as chemoresistance of GSRCC,continue to be crucial areas of ongoing research,whose directions are closely tied to advancements in molecular biology research on GSRCC.
文摘BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours,such as lung cancer,oesophageal cancer or mediastinum tumours.Renal cell carcinoma(RCC),accounting for 2%to 3%of all tumours,is a common malignant tumour of the urinary system.Renal clear cell carcinoma(RCCC)constitutes the predominant pathological subtype of RCC,comprising approximately 70%to 80%of all RCC cases.RCCC can spread and metastasise through arterial,venous and lymphatic circulation to almost all organs of the body.Moreover,lung,bone,liver,brain and local recurrence are the most common metastatic neoplasms of RCCC.However,EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer.CASE SUMMARY A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough.The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung,and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe.Therefore,the patient underwent thoracoscopic left superior lobe wedge resection,and pathology confirmed EBM from the RCCC.CONCLUSION EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage.If a bronchial tumour is found in a patient with RCCC,the possibility of bronchial metastatic cancer should be considered.
文摘Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study aimed to identify differences in the proliferative indices among variants of cBCC and cSCC diagnosed at a tertiary healthcare center. Method: Skin biopsies histologically diagnosed as cBCC and cSCC between 2012 and 2018 at the Federal Medical Centre (FMC) Umuahia, Abia State, Nigeria, were analyzed. Archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were retrieved along with clinical data, and were prepared on charged microscope slides and the immunohistochemical staining was carried out. The primary antibody used in this study was clone BioCare CRM325C (RM) and adenotonsillar tissue blocks/slides served as positive controls. Ki-67 immunohistochemistry was performed on fresh 4µm sections of the tumor specimens. Results: The application of Ki-67 immunoperoxidase on both BCC and SCC cohort, yielded an intense observable brownish nuclear stain in areas of dense proliferating tumour cells on both cutaneous tumours. The average Ki-67 index for all cSCC cases was 24.7%, with a range of 2.3% - 80%, while the mean for cBCC was 15.8%, ranging from 1.2% - 45.6%. Variants with high proliferative indices were observed in 11.9% of cBCC cases and 29.1% of cSCC cases. Among the low proliferative index category, cSCC accounted for 5.4%, while cBCC represented 14.3%. For mild proliferative indices, cSCC cases made up 7.3% and cBCC, 11.9%. The majority of cases showed moderate proliferative indices, with 61.9% for cBCC and 58.2% for cSCC. Overall, there was a significant difference in proliferative indices between cSCC, cBCC, and their variants. Conclusion: The study found a significantly higher rate of cell proliferation, measured by Ki-67 immunostaining, in cSCC and its variants compared to cBCC. However, certain variants of cBCC also exhibited high Ki-67 expression, indicating they can be as aggressive as some cSCC variants.
基金Supported by Xi’an Municipal Health Commission of China,No.2022qn07 and No.2023ms11.
文摘As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.
基金Supported by Foundation of Henan Educational Committee,No.22A310024and Natural Science Foundation for Young Teachers'Basic Research of Zhengzhou University,No.JC202035025。
文摘Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.
文摘BACKGROUND Cases of severe inflammatory renal disease and renal cell carcinoma(RCC)that occur simultaneously in the same kidney have been occasionally reported.However,extrarenal RCC that does not originate from the native kidney has rarely been reported.To our knowledge,this is the first reported case of RCC developing in the ipsilateral retroperitoneal space after a simple nephrectomy(SN)for inflammatory renal disease.CASE SUMMARY A 63-year-old woman was referred to our hospital following the incidental discovery of a left retroperitoneal mass without specific symptoms.Her medical history revealed a left SN 27 years ago due to a renal abscess.Magnetic resonance imaging of the abdomen revealed three oval masses in the left retroperitoneum.The masses were successfully excised,and subsequent pathology confirmed papillary RCC.After surgery,the patient remained disease-free for 11 years without adjuvant therapy.CONCLUSION Clinicians should be vigilant of RCC in patients with retroperitoneal masses,especially after SN for inflammatory renal disease.
基金The Research fund from the Chosun University Hospital,No.2023-26.
文摘BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts,often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage.A total of 38 kidneys were excised from 19 patients,with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months.Eight patients underwent open nephrectomies,and 11 underwent hand-assisted laparoscopic nephrec-tomies.RCC was detected in 15.8%of kidneys,affecting 21.1%of patients.Two patients had multifocal RCC in both kidneys.All RCC cases were pT1 stage,with the largest lesion averaging 16.5 mm in diameter.The average operative duration was 120 minutes,with intraoperative blood loss averaging 184.2 mL.Five patients required blood transfusions.Postoperative complications occurred in five patients,with a mean hospital stay of 17.1 days.The mean follow-up period was 28.1 months.CONCLUSION The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone.Thus,clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD,particularly those on dialysis.
文摘Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.
基金supported by grants from National Natural Science Foundation of China(no.:82174020 and no.:31301137)Shanxi Basic Research Program of China(202103021224378)Shanxi Bethune Hospital Talent Introduction Research Start-up Fund of China(2022RC13)。
文摘Background:The role of Claudin-1 in tongue squamous cell carcinoma(TSCC)metastasis needs further clarification,particularly its impact on cell migration.Herein,our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms.Methods:36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1.Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells.Claudin-1 knockdown cell lines were established using short hairpin RNA transfection.Migration effects were assessed through wound healing assays.Furthermore,the expression of EMTassociated molecules was measured via western blotting.Results:Claudin-1 expression decreased as TSCC malignancy increased.Adenosine monophosphate–activated protein kinase(AMPK)activation led to increased Claudin-1 expression and membrane translocation,inhibiting TSCC cell migration and epithelial–mesenchymal transition(EMT).Conversely,Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation.Conclusions:Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.
文摘Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.
基金the National Natural Science Foundation of China(Grant No.:51803120).
文摘Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.
文摘Objective:two new cases of temporal bone squamous cell carcinoma(TBSCC)with a bilateral occurrence are presented.Furthermore,a review of the literature was performed and the yearly incidence was calculated.Methods:A systematic review of the literature was conducted using PRISMA guidelines.Results:Twenty-two more cases were found in literature.With a total of 24 cases,the calculated yearly incidence of bilateral TBSCC is 49:10^12 A history of chronic otitis or regional radiotherapy was found in respectively 50%and 12%of patients.In nine patients,the tumors developed synchronously(within 6 months)and in 13 metachronously.Conclusions:The calculated incidence is 89 times higher than mathematically expected considering the incidence of unilateral cases.An explanation might be a history of chronic otitis or prior radiotherapy.The tumor staging of both the first tumor group and the contralateral tumor group are similar to unilateral temporal bone squamous cell carcinoma series.
基金Supported by The Medical Talents of Wuhan Hospital of Traditional Chinese and Western Medicine,No.202212001Hubei Natural Science Foundation,No.2023AFB1091 and No.2023AFB988+2 种基金The 7th Wuhan Young and Middle-Aged Backbone Talent of Medical Training ProjectNo.2019-87The Research Projects of Biomedical Center of Hubei Cancer Hospital,No.2022SWZX19.
文摘BACKGROUND The early diagnosis rate of esophageal cancer(EC),one of the most prevalent digestive tract cancers worldwide,remains low.AIM To investigate the utility of plasma SHOX2,SEPTIN9,EPO,and RNF180 methylation in the clinical diagnosis and monitoring of EC.Plasma samples were collected from 210 patients at Hubei Cancer Hospital,and TaqMan polymerase chain reaction was employed to detect plasma SHOX2,SEPTIN9,RNF180,and EPO methylation.The area under the curve was used to estimate their diagnostic value for EC.Cox and logistic regression analyses were used to estimate the independent screening risk factors for patients with EC.RESULTS The sensitivity and specificity of combined assessment of plasma SHOX2,SEPTIN9,RNF180,and EPO methylation for adenocarcinoma,squamous cell carcinoma(SCC),and EC detection were 66.67%and 86.27%,77.40%and 85.29%,and 76.19%and 86.27%,respectively;the area under the curve values for diagnosing adenocarcinoma,SCC,and EC were 0.737[95%confidence interval(CI):0.584–0.89],0.824(95%CI:0.775–0.891),and 0.864(95%CI:0.809–0.92),respectively.CONCLUSION According to our findings,plasma SHOX2,SEPTIN9,RNF180,and EPO methylation exhibits appreciated sensitivity for diagnosing EC.The precise measurement of plasma SHOX2,SEPTIN9,RNF180,and EPO methylation can improve EC diagnosis and therapy efficacy monitoring.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009ATianjin Medical University Cancer Hospital National Natural Science Foundation Cultivation Program,No.220108+3 种基金National Natural Science Foundation of China,No.82373134Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2022KJ228Chinese Anti-Cancer Association-Heng Rui Anti-angiogenesis Targeted Tumor Research Fund,No.2021001045and Scientific Research Translational Foundation of Wenzhou Safety(Emergency)Institute of Tianjin University,No.TJUWYY2022025.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.
文摘Objective:This review aimed to summarize the role of the Hippo signaling pathway in renal cell carcinoma (RCC), a urologic malignancy with subtle initial symptoms and high mortality rates due to metastatic RCC. The Hippo signaling pathway, which regulates tissue and organ sizes, plays a crucial role in RCC progression and metastasis. Understanding the involvement of the Hippo signaling pathway in RCC provides valuable insights for the development of targeted therapies and improved patient outcomes.Methods:In this review, we explored the impact of the Hippo signaling pathway on RCC. Through an analysis of existing literature, we examined its role in RCC progression and metastasis. Additionally, we discussed potential therapeutic strategies targeting the Hippo pathway for inhibiting RCC cell growth and invasion. We also highlighted the importance of investigating interactions between the Hippo pathway and other signaling pathways such as Wnt, transforming growth factor-beta, and PI3K/AKT, which may uncover additional therapeutic targets.Results:The Hippo signaling pathway has shown promise as a target for inhibiting RCC cell growth and invasion. Studies have demonstrated its dysregulation in RCC, with altered expression of key components such as yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ). Targeting the Hippo pathway has been associated with suppressed tumor growth and metastasis in preclinical models of RCC. Furthermore, investigating crosstalk between the Hippo pathway and other signaling pathways has revealed potential synergistic effects that could be exploited for therapeutic interventions.Conclusion:Understanding the role of the Hippo signaling pathway in RCC is of paramount importance. Elucidating its functions and molecular interactions contributes to RCC diagnosis, treatment, and the discovery of novel mechanisms. This knowledge informs the development of innovative therapeutic strategies and opens new avenues for research in RCC. Further investigations are warranted to fully comprehend the complex interplay between the Hippo pathway and other signaling pathways, ultimately leading to improved outcomes for RCC patients.
文摘BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.
基金supported by the Scientific Research and Innovation Team of Hebei University(IT2023B07)the Natural Science Foundation of Hebei Province(F2023201069)the Postgraduate’s Innovation Fund Project of Hebei University(HBU2024BS021).
文摘Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.
文摘Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.